Intrauterine growth restriction, soluble fms-like tyrosine kinase-1 to placental growth factor ratio increase and preeclampsia.

BACKGROUND: Intrauterine growth restriction (IUGR) and preeclampsia (PE) share common features such as ischemic placental disease but also differ in their clinical expression regarding maternal diseases. The reason why IUGRremains isolated in some cases yet is followed by clinical manifestations of PE in other cases remains unexplained. CASE REPORT: A 40-year old woman, gravida two, para one, experienced early-onset IUGR with a significant increase in the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) but, surprisingly, without any maternal clinical manifestations of PE. CONCLUSION: IUGR and a significant increase in sFlt-1/PlGF ratio without PE raise the issue of a missing factor enabling IUGR, a significant increase in sFlt-1/PlGF ratio, and PE to be linked. TEACHING POINTS: (1) Early-onset IUGR and a significant increase in sFlt-1/PlGF ratio do not necessarily mean the onset of PE. (2) Combining early-onset IUGR and a significant increase in sFlt-1/PlGF ratio without PE raises the question of an additional factor responsible for the onset of PE.

Semilobar holoprosencephaly prenatal diagnosis: an unexpected complex rearrangement in a de novo apparently balanced reciprocal translocation on karyotype.

We report a semilobar holoprosencephaly (HPE) in a post-intracytoplasmic-sperm-injection pregnancy. It was suggested by ultrasonography (US), documented on karyotype, identified with magnetic resonance imaging (MRI), established after birth and confirmed on post-mortem autopsy. An amniocentesis revealed a de novo apparently balanced reciprocal translocation 46,XY, t(7;8) (q31.3;q12). Fluorescence in situ hybridization (FISH) identified a deletion in the region of the Sonic Hedgehog gene (SHH) on der(8); nevertheless, the subtelomeric regions for chromosomes 7 and 8 were present. The parents decided to continue the pregnancy; a boy was born and survived for 3 days. The brain autopsy confirmed the semilobar HPE previously noted on US and MRI. Further, band-specific FISH revealed, in addition to SHH deletion, the presence of an inversion in the 7q translocated material on der(8). The parents' karyotypes were normal. An unexpected complex rearrangement was present in a de novo apparently balanced reciprocal translocation in a semilobar HPE.

Prospective evaluation of uterine artery flow velocity waveforms at 12-14 and 22-24 weeks of gestation in relation to pregnancy outcome and birth weight.

OBJECTIVE: Uterine artery flow velocity was prospectively assessed using Doppler ultrasound at 12-14 and 22-24 weeks of gestation in the prediction of subsequent complications related to uteroplacental insufficiency: preeclampsia, pregnancy-induced hypertension, fetal growth restriction, fetal death and placental abruption, and to elucidate its relationship with birth weight. METHODS: Uterine artery Doppler assessment was obtained during routine ultrasound screening in 263 unselected women. Flow velocity waveforms were coded according to the number of notches present at each scanning, respectively: none (0, 0), uni-/bilateral notches that disappeared (1, 0) or (2, 0), uni-/bilateral notches that persisted unilaterally (1, 1) or (2, 1), and persistent bilateral notches (2, 2). RESULTS: Complete outcome data was obtained for 243 (92.4%) women. Of these women, 55 (22.6%) and 84 (34.6%) women had uni- and bilateral notches, respectively, at 12-14 weeks' gestation; 14 (5.8%) and 21 (8.6%) patients had uni- and bilateral notches, respectively, at 22-24 weeks' gestation. Analysis of complication rates for the four groups showed that they increased with notch persistence (5.7, 13.5, 57.1 and 76.2%), while the corresponding mean birth weight declined (3,273, 3,180, 2,698 and 2,418 g). CONCLUSION: The absence or early disappearance of uterine artery notches is associated with fewer complications related to uteroplacental insufficiency and normal birth weight, whereas their late and partial disappearance or bilateral persistence tends to compromise the prognosis.

Structural chromosomal mosaicism and prenatal diagnosis.

True structural chromosomal mosaicism are rare events in prenatal cytogenetics practice and may lead to diagnostic and prognostic problems. Here is described the case of a fetus carrying an abnormal chromosome 15 made of a whole chromosome 2p translocated on its short arm in 10% of the cells, in association with a normal cell line. The fetal karyotype was 46,XX,add(15)(p10).ish t(2;15)(p10;q10)(WCP2+)[3]/46,XX[27]. Pregnancy was terminated and fetus examination revealed a growth retardation associated with a dysmorphism including dolichocephaly, hypertelorism, high forehead, low-set ears with prominent anthelix and a small nose, which were characteristic of partial trisomy 2p. Possible aetiologies for prenatal mosaicism involving a chromosomal structural abnormality are discussed.

[Uteroplacental haemodynamics and uterine artery Doppler practice at 12 weeks gestation]. / Hémodynamique utéroplacentaire et pratique du Doppler utérin à 12 semaines d'aménorrhée.

Last years, feasibility and possible interest of uterine artery Doppler during the third month of gestation were confirmed. Doppler flow velocity waveforms can be obtained and assessed in both uterine arteries using abdominal ultrasonography at 12-14 weeks' gestation. The no notch group (one third of women) has a low risk for hypertension, intra-uterine growth restriction, abruptio placentae. The "protecting" effect of the absence of uterine artery notch is as high as this physiological change occurs earlier.

Ultrasound assessment in a case of sialic acid storage disease.

A woman was referred to our unit at 25 weeks' gestation because of fetal ascites. Conventional and three-dimensional ultrasound examinations revealed coarse facies and micromelia which strongly suggested storage disease, despite the absence of an index familial case. Amniocentesis was performed and, in view of the poor prognosis, the pregnancy was terminated. Autopsy confirmed all the sonographic features and the cultured amniocytes confirmed the diagnosis of infantile sialic acid storage disease.

First-trimester diagnosis of sirenomelia. A case report.

We report a case of sirenomelia diagnosed at 13 gestational weeks. This rare malformation sequence is characterized by fusion and rotation of the lower limbs to various degrees and anorectal atresia, usually associated with absence of bladder and agenesis or dysgenesis of the kidneys. Diagnosis is commonly made later in the second trimester of pregnancy with oligohydramnios as the alerting sign. Survival is extremely rare, and only possible in the absence of bilateral renal agenesis. In view of the dismal prognosis, early diagnosis allows for earlier and less traumatic therapeutic abortion.

Metabolic studies in a patient with severe carnitine palmitoyltransferase type II deficiency.

Here we report on a patient with severe ("non-classic") carnitine palmitoyltransferase type II (CPT II) deficiency. Hypoglycemia prompted by an infectious episode and associated with non-ketotic dicarboxylic aciduria orientated diagnosis towards beta-oxidation deficiency disorders. Blood carnitine levels revealed a secondary carnitine deficiency that was responsive to oral L-carnitine supplementation. Blood acylcarnitine profiles were abnormal and included acetyl (C2:0), butyryl/isobutyryl (C4:0), isovaleryl/2-methylbutyryl (C5:0), hexanoyl (C6:0), myristoyl (C14:0), palmitoyl (C16:0), hexadecenoyl (C16:1), oleyl (C18:1) and stearoyl (C18:0) carnitine. In urine, excess excretion of dicarboxylylcarnitines, mainly dodecanedioylcarnitine, was noticed. Upon carnitine supplementation, C8 to C12 fatty acylcarnitines, with decanoylcarnitine as well as C10 to C14 dicarboxylylcarnitines being prominent, were observed in urine. Biochemical measurements disclosed a severe reduction of mitochondrial CPT II activity (7% of normal values). Correlations of metabolic findings in the patient and physiological roles of CPT II are briefly discussed.

Mitochondrial very long chain acyl-CoA dehydrogenase deficiency--a new disorder of fatty acid oxidation.

Very long chain acyl-CoA dehydrogenase is a newly characterised enzyme in mitochondrial fatty acid oxidation. A girl who presented on the second day of life with a sudden and severe illness due to deficiency of this enzyme is reported. There is evidence that some children (and perhaps all) originally diagnosed with a deficiency of long-chain acyl-CoA dehydrogenase, in fact, have a defect involving very long chain acyl-CoA dehydrogenase.

Point mutation of the mitochondrial tRNA(Leu) gene (A 3243 G) in maternally inherited hypertrophic cardiomyopathy, diabetes mellitus, renal failure, and sensorineural deafness.

The A 3243 G mutation of the mitochondrial tRNA(Leu) gene was found to segregate with maternally inherited diabetes mellitus, sensorineural deafness, hypertrophic cardiomyopathy, or renal failure in a large pedigree of 35 affected members in four generations. Presenting symptoms almost consistently involved deafness and recurrent attacks of migraine-like headaches, but the clinical course of the disease varied within and across generations. The A 3243 G mutation has been previously reported in association with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome (MELAS) and with diabetes mellitus and deafness. To our knowledge, however, hypertrophic cardiomyopathy is not a common feature in people with the A 3243 G mutation and renal failure has not been hitherto reported in association with this mutation. The present observation gives additional support to the variable clinical expression of mtDNA mutations in humans.

Diagnosis of peroxisomal disorders by analysis of phytanic and pristanic acids in stored blood spots collected at neonatal screening.

Concentrations of phytanic acid and pristanic acid were measured in stored dried blood spots collected at neonatal screening from patients with peroxisomal disorders, and compared with concentrations in control blood spots. In blood spots from two patients with Zellweger syndrome both phytanic acid and pristanic acid concentrations were increased but their concentration ratio was normal. In the blood spot from a patient with rhizomelic chondrodysplasia punctata, the concentration of phytanic acid was increased, whereas pristanic acid was within the control range, resulting in a low pristanic acid/phytanic acid ratio. In the blood spot from a patient with X-linked adrenoleukodystrophy, the concentrations of the acids and their ratio were normal. These findings are consistent with results for these acids in plasma from such patients. Measurement of phytanic acid and pristanic acid and their ratios in stored dried blood collected at neonatal screening can therefore be used in the diagnosis of peroxisomal disorders, especially for those cases in which, owing to early death of the patient, no other material is available for biochemical investigations.

[Embryofetopathy of the newborn infant of a phenylketonuric mother. A diagnosis not to be missed]. / L'embryofoetopathie du nouveau-né de mère phénylcétonurique. Un diagnostic à ne pas manquer.

Children with phenylketonuria (PKU) detected in the neonatal period and who have received the appropriate diet develop normally whatever their sex. However, female PKU patients who, before becoming pregnant, do not take the precaution to follow a diet bringing phenylalanine to "normal levels" (2 to 5 mg in 100 ml of blood) give birth to children presenting with severe embryofoetal damage (e.g. intrauterine growth retardation, microcephaly, mental retardation, various malformations) directly due to their hyperphenylalaninaemia (20 mg or more in 100 ml of blood under a free diet). It is important to know these facts, since the benefits of systematic neonatal PKU detection may be cancelled by this late complication. The therapeutic approach in such cases is a follows: 1. Young women with known PKU must be informed of this risk and how it can be avoided by a preconception therapeutic diet. This means that they must permanently reside in the same geographical area, receive an adequate information at the end of puberty, use and effective contraception method and program their pregnancies preceded by a return to low phenylalanine diet. 2. Doctors must remember that because PKU detection has not become systematic until 1978, PKU girls of child-bearing are remain undetected, that they are not always mentally debilitated and can normally five birth to children with embryofoetal damage. In case of e.g. unexplained intrauterine growth retardation or microcephaly, it is necessary to perform a Guthrie test on the woman, since a prenatal diagnosis may lead to therapeutic abortion, and a postnatal diagnosis to a genetic counselling which will avoid recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)